17-8369325-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001304947.3(KRBA2):​c.1042G>A​(p.Val348Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

KRBA2
NM_001304947.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
Variant links:
Genes affected
KRBA2 (HGNC:26989): (KRAB-A domain containing 2) Predicted to enable nucleic acid binding activity. Predicted to be involved in DNA integration and regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15806079).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRBA2NM_001304947.3 linkc.1042G>A p.Val348Met missense_variant Exon 2 of 2 ENST00000396267.3 NP_001291876.1 Q6ZNG9A8MX02
KRBA2NM_213597.3 linkc.1288G>A p.Val430Met missense_variant Exon 2 of 2 NP_998762.1 Q6ZNG9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRBA2ENST00000396267.3 linkc.1042G>A p.Val348Met missense_variant Exon 2 of 2 2 NM_001304947.3 ENSP00000379565.3 A8MX02
ENSG00000263809ENST00000582471.1 linkn.*2025G>A non_coding_transcript_exon_variant Exon 6 of 6 5 ENSP00000463847.1 J3QQQ9
ENSG00000263809ENST00000582471.1 linkn.*2025G>A 3_prime_UTR_variant Exon 6 of 6 5 ENSP00000463847.1 J3QQQ9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251484
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000487
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1288G>A (p.V430M) alteration is located in exon 2 (coding exon 2) of the KRBA2 gene. This alteration results from a G to A substitution at nucleotide position 1288, causing the valine (V) at amino acid position 430 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
.;T;T;T;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.058
N
LIST_S2
Benign
0.65
.;T;T;.;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.16
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
.;.;N;N;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.5
.;N;N;.;.
REVEL
Benign
0.053
Sift
Uncertain
0.014
.;D;D;.;.
Sift4G
Uncertain
0.033
.;D;D;.;.
Polyphen
0.94
.;.;P;P;.
Vest4
0.16, 0.20
MutPred
0.48
.;.;Gain of disorder (P = 0.0437);Gain of disorder (P = 0.0437);.;
MVP
0.21
MPC
0.61
ClinPred
0.18
T
GERP RS
1.7
Varity_R
0.098
gMVP
0.10

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764138898; hg19: chr17-8272643; API